A settlement of payment of US $ 2.5 billion by a US-based multinational pharmaceutical company to around 8000 patients who used or using articular surface replacement medical device is viewed as one of the highest medical compensations. Though the device was withdrawn from the market in 2010 itself, the multinational company Johnson and Johnson has now reached on this settlement. The apex regulatory authority, Central Drugs Standard Control Organization (CDSCO), Government of India, too has issued an alert - Medical device alert, dated December 9, 2013 - on this DePuy ASR hip replacement implants. After three years of withdrawal of the device, this alert of Government looks too late and raised several concerns as the company has made no attempt so far to compensate Indian users reasonably. The Government urged not to use the DePuy ASR hip replacement implants, to return the unused ones, and to continue monitoring the patients who are with these implants.
The articular surface replacement (ASR) is a ‘metal on metal’ hip introduced as an alternative to metal head with a polyethylene cup. Metal cup was thought to be more durable than the plastic cup. It was used in hip replacement surgeries for people with hip joint damage from arthritis or injuries. DePuy Orthopaedics, a subsidiary of American multinational pharmaceutical company Johnson and Johnson, introduced this ASR hip prosthesis and sold more than 93,000 such implants globally. Some 35,000 people in USA were given this artificial hip. Government of India claimed that 15,829 such ASR implants were imported to the country and 1295 unused implants were returned to the company. This shows that more than 14 thousand persons in our country are given these implants. It was believed that DePuy ASR would provide greater mobility and help patients get back on their feet quicker.
There are two forms of DePuy ASR: ASR XL (total hip replacement) and ASR resurfacing (hip resurfacing) and both forms were introduced into Europe in 2003. However, US FDA did not approve ASR resurfacing. Being ASR resurfacing a new technique, US FDA wanted the clinical study report before approval. Before approving for marketing in Europe, no clinical study was conducted to ensure that the device works and causes no health concern. The company could not support or answer the safety questions raised by the US FDA and it was never approved for use in USA. Unfortunately, the device found its access to US market as off label use. Off label use is illegal. Often commented, the off label use means there is no enough evidence or data to support such claim.
Within two years of introduction of ASR, the side effects of the devices started to appear. After several years, now it is known to have caused several side effects to the patients. The reaction resulted from metal debris that destroys the soft tissues surrounding the joints and left some patients with long term disability. Initially this condition may be painless, but if untreated may lead to pain and swelling around the joint and could damage some of the muscles, bones and nerves around the hip. The cobalt and chromium metal is released from ASR into the patient’s blood and cerebrospinal fluids causing abnormally high toxic level of these ions in blood. Besides, it required the early revision of surgery which put the patient in another risk of anaesthesia and higher risk of fracture of the revision. The long term effects are unknown. The US FDA recommended that the patients should be monitored for systemic effects particularly cardiovascular, neurological, and renal and thyroid signs and symptoms. There is also apprehension that metal hip replacement may cause increased DNA changes which might result in genotoxicity in patients.
Throughout the marketing period, the company continued denial that the side effects were due to the faulty devices but attributed them to the faulty surgery. The company while recalling the device from global markets cited the reason as commercial rather than of any health concern. There have been large numbers of legal suits in USA claiming compensation for injury due to use of the faulty ASR. On 19th November 2013, it was reported that Johnson and Johnson agreed for a settlement of $2.5 billion for an estimated 8000 cases. If the settlement works each patient will get $250,000 (currently this is approximately Rs.150 lakh). The agreement needs the acceptance by 90 per cent of eligible claimants to move forward for implementation. Unfortunately, no such provision is made by the company to compensate the Indian patients suffered from the faulty ASR. Multinational companies always treated poor and developing countries differently from the rich and developed countries. They have used one philosophy or standard for poor and developing countries and the other for the advanced ones. However, Maharashtra government’s request for a CBI inquiry into the whole issue is a welcome step. The late warning by CDSCO in this case raised some doubt in people’s mind on CDSCO’s role. If the company has recalled the devices from market in 2010, why wide publicity of this recall was not given? What was CDSCO doing?
There is no separate regulation for medical devices in our country. They have been treated as drugs under Drugs and Cosmetics Act. As they are specialised substances requiring different scope of regulation, the Government of India currently proposed to have separate section in the Drugs and Cosmetics Act for regulating them. However, due to current political and other scenario including the observations of the Parliamentary Committee, it seems impossible to have the Drugs and Cosmetics (Amendment) Act 2013 a reality. Nevertheless, the CDSCO can strengthen its expertise and continue regulating. Being the protector of public health, it should act as quickly as possible especially issuing alert to minimise the damage or harm.
While the introduction of ASR was viewed as giant step advancement in joint replacement, unfortunately the metal hips made the user sick due to disintegration of metals. As there was no regulatory requirement of clinical testing of medical devices before approval for marketing, the ASR device was introduced with just laboratory testing on simulated model. Perhaps, a stronger regulation on medical devices, implementing a Pharmacovigilance programme and timely action of the authorities may prevent the occurrence of ASR type disaster and protect the Indians from unnecessary risk arise out of use of medicines or medical devices!
(The authors are with Department of Pharmacy, Annamalai University, Annamalai Nagar, Tamil Nadu 608 002)